Protein Glycosylation: Implications for In Vivo Functions and Therapeutic Applications

Bhatia, Prakash K.; Mukhopadhyay, Asok

doi:10.1007/3-540-49811-7_5

Cited by 24 publications

(23 citation statements)

References 251 publications

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“…in cell adhesion, cell-to-cell communication, and immune response (8). Glycosylation is also very important for targeting of proteins to various compartments of the cells.…”

mentioning

confidence: 99%

N-linked (N-) Glycoproteomics of Urimary Exosomes*

Saraswat

Joenväära

Musante

et al. 2015

Molecular & Cellular Proteomics

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Epithelial cells lining the urinary tract secrete urinary exosomes (40 -100 nm) that can be targeted to specific cells modulating their functionality. One potential targeting mechanism is adhesion between vesicle surface glycoproteins and target cells. This makes the glycopeptide analysis of exosomes important. Exosomes reflect the physiological state of the parent cells; therefore, they are a good source of biomarkers for urological and other diseases. Moreover, the urine collection is easy and noninvasive and urinary exosomes give information about renal and systemic organ systems. Accordingly, multiple studies on proteomic characterization of urinary exosomes in health and disease have been published. However, no systematic analysis of their glycoproteomic profile has been carried out to date, whereas a conserved glycan signature has been found for exosomes from urine and other sources including T cell lines and human milk.Here, we have enriched and identified the N-glycopeptides from these vesicles. These enriched N-glycopeptides were solved for their peptide sequence, glycan composition, structure, and glycosylation site using collision-induced dissociation MS/MS (CID-tandem MS) data interpreted by a publicly available software GlycopeptideId. Released glycans from the same sample was also analyzed with MALDI-MS.We have identified the N-glycoproteome of urinary exosomes. In total 126 N-glycopeptides from 51 N-glycosylation sites belonging to 37 glycoproteins were found in our results. The peptide sequences of these N-glycopeptides were identified unambiguously and their glycan composition (for 125 N-glycopeptides) and structures (for 87 Nglycopeptides) were proposed. A corresponding glycomic analysis with released N-glycans was also performed. We identified 66 unique nonmodified N-glycan compositions and in addition 13 sulfated/phosphorylated glycans were also found. This is the first systematic analysis of Nglycoproteome of urinary exosomes. Molecular & Cellular Proteomics

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“…in cell adhesion, cell-to-cell communication, and immune response (8). Glycosylation is also very important for targeting of proteins to various compartments of the cells.…”

mentioning

confidence: 99%

N-linked (N-) Glycoproteomics of Urimary Exosomes*

Saraswat

Joenväära

Musante

et al. 2015

Molecular & Cellular Proteomics

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“…In this capacity, through interactions with proteins, complex glycans modulate a variety of biological processes including pathogen recognition, innate and acquired immunity (Alexopoulou, et al, 2007; Crocker, et al, 2007; Rudd, et al, 2004; van Die and Cummings, 2006), glycoprotein targeting (Bhatia and Mukhopadhyay, 1999; Helenius and Aebi, 2004; Varki, et al, 2008), and adhesion (Kawashima, et al, 2005; Lowe, 2002; Taylor and Drickamer, 2007; Wang, et al, 2005) and trafficking (Crocker, 2005; Smithson, et al, 2001). Obtaining a complete picture of a biological process or understanding higher-level organization of a biological system accordingly requires decoding protein-glycan interactions.…”

Section: Introductionmentioning

confidence: 99%

Context-Specific Target Definition in Influenza A Virus Hemagglutinin-Glycan Receptor Interactions

Shriver

Raman

Viswanathan

et al. 2009

Chemistry & Biology

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Summary Protein-glycan interactions are important regulators for a variety of biological processes, ranging from immune recognition to anticoagulation. An important area of active research is directed towards understanding the role of host cell surface glycans as recognition sites for pathogen protein receptors. Recognition of cell surface glycans is a widely employed strategy for a variety of pathogens, including bacteria, parasites, and viruses. We present here a representative example of such an interaction: the binding of influenza A hemagglutinin (HA) to specific sialylated glycans on the cell surface of human upper airway epithelial cells, which initiates the infection cycle. We detail a generalizable strategy to understand the nature of protein-glycan interactions both structurally and biochemically, using HA as a model system. This strategy combines a top-down approach using available structural information to define important contacts between glycans and HA, with a bottom-up approach using data mining and informatics approaches to identify the common motifs which distinguish glycan binders from non-binders. By probing protein-glycan interactions simultaneously through top-down and bottom-up approaches we can scientifically validate a series of observations. This in turn provides additional confidence and surmounts known challenges in the study of protein-glycan interactions, such as accounting for multivalency, and thus truly defines concepts such as specificity, affinity, and avidity. With the advent of new technologies for glycomics—including glycan arrays, data mining solutions, and robust algorithms to model protein-glycan interactions—we anticipate that such combination approaches will become tractable for a wide variety of protein-glycan interactions.

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“…These values contrasted with relative molar ratios of standard O-glycans (molar ratios ϭ 1:1:2; supplemental Fig. S2) (37,38). In particular, the relative concentration of sialic acid Neu5Ac was lower than expected.…”

Section: Homology Model Of Hil-11-mentioning

confidence: 63%

“…These values compared favorably with the composition of triantennary N-glycans 1:5: 3:3:3 (supplemental Fig. S2) (37,38). Moreover, the molar ratio between N-glycan and N T -3N interleukin determined in the assay was 0.9 (taking fucose as reference), which demonstrated that in average each molecule of interleukin had incorporated, about one N-glycan moiety.…”

Section: Homology Model Of Hil-11-mentioning

confidence: 68%